TY  - JOUR
AU  - Bedrosian, Tracy A
AU  - Houtman, Judith
AU  - Eguiguren, Juan Sebastian
AU  - Ghassemzadeh, Saeed
AU  - Rund, Nicole
AU  - Novaresi, Nicole M
AU  - Hu, Lauren
AU  - Parylak, Sarah L.
AU  - Denli, Ahmet M
AU  - Randolph-Moore, Lynne
AU  - Namba, Takashi
AU  - Gage, Fred H
AU  - Toda, Tomohisa
TI  - Lamin B1 decline underlies age‐related loss of adult hippocampal neurogenesis
JO  - The EMBO journal
VL  - 40
IS  - 3
SN  - 1460-2075
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2021-00551
SP  - e105819
PY  - 2021
AB  - Neurogenesis in the adult hippocampus declines with age, a process that has been implicated in cognitive and emotional impairments. However, the mechanisms underlying this decline have remained elusive. Here, we show that the age-dependent downregulation of lamin B1, one of the nuclear lamins in adult neural stem/progenitor cells (ANSPCs), underlies age-related alterations in adult hippocampal neurogenesis. Our results indicate that higher levels of lamin B1 in ANSPCs safeguard against premature differentiation and regulate the maintenance of ANSPCs. However, the level of lamin B1 in ANSPCs declines during aging. Precocious loss of lamin B1 in ANSPCs transiently promotes neurogenesis but eventually depletes it. Furthermore, the reduction of lamin B1 in ANSPCs recapitulates age-related anxiety-like behavior in mice. Our results indicate that the decline in lamin B1 underlies stem cell aging and impacts the homeostasis of adult neurogenesis and mood regulation.
KW  - Aging: genetics
KW  - Aging: metabolism
KW  - Animals
KW  - Anxiety: genetics
KW  - Cell Differentiation
KW  - Cell Line
KW  - Disease Models, Animal
KW  - Down-Regulation
KW  - Female
KW  - Hippocampus: cytology
KW  - Hippocampus: metabolism
KW  - Lamin Type B: genetics
KW  - Lamin Type B: metabolism
KW  - Male
KW  - Mice
KW  - Neural Stem Cells: cytology
KW  - Neural Stem Cells: metabolism
KW  - Neurogenesis
KW  - Rats
LB  - PUB:(DE-HGF)16
C6  - pmid:33300615
C6  - 33300615
C2  - pmc:PMC7849303
DO  - DOI:10.15252/embj.2020105819
UR  - https://pub.dzne.de/record/155271
ER  -